The present invention is directed to a transdermal (or percutaneous) delivery system for piroxicam. This delivery system is a drug-containing adhesive device which has a constant release rate over a period of time.
Piroxicam is a non-steroidal anti-inflammatory drug and used as an effective analgesic and anti-inflammatory agent in rheumatoid arthritis, osteoarthritis and acute pain in musculoskeletal disorders and acute gout. It has been known to be an effective analgesic in fracture, dental, postoperative and postpartum pain. It is about equal in potency to indomethacin as an inhibitor of prostaglandin biosynthesis in vitro.
Piroxicam is used generally orally. Although piroxicam has a strong therapeutic effect, it causes side effects such as gastro-intestinal trouble, peptic ulcer. Orally administered piroxicam is metabolized at the first pass route. Less than 5% of the drug is excreted in the urine unchanged. The metabolite is at least 1000 times less active than piroxicam inhibiting prostaglandin synthesis.
The potential advantage of delivering piroxicam transdermally is that gut wall and hepatic metabolism and the gastrointestinal reaction may be avoided.
Transdermal delivery system eliminates the first pass effects and allows a controlled amount of the active substance such as piroxicam to be continuously administered over a sustained period of time.
Francoeur et al., U. S. patent application Ser. No. 925,641(Oct. 31, 1986), disclose topical compositions of amlodipine, doxazosin, glipizide, piroxicam and other drugs containing aqueous solution of ethanol, 1-alkylazacycloheptane-2-one and oleic aicd. However, this method is impossible to make a thin patch and is only possible to make gel, ointment and liquid compositions.
In Japanese, Laid-Open Patent Ser. No. 91-251534, there is disclosed patch compositions for increased dermal penetration of piroxicam by adding penetration enhancer, selected from polyoxyethylenealkyl ethers or alkanolamides, and dissolving assitant agent of polyvinypyrrolidone to pressure-sensitive adhesives of copolymer of vinylpyrrolidone and methacrylic ester. However, this composition is also inferior in percutaneous absorption because polyvinylpyrrolidone of dissolving agent acts only a dissolving assistant role and does not assist the absorption of drug.
For the reasons mentioned above, as result of concentrative researches about the improvement of percutaneous absorption and high content of drug in patch, the present inventors found that, in case of using certain absorption assitants, the excessively dissolved piroxicam is included in matrix and simultaneously the percutaneous absorbability is surprisingly enhanced, so that have been perfected the present invention.